Inhibition of the Renin-Angiotensin System Improves Response to Neoadjuvant Therapy in Patients With Liver Metastasis of Colorectal Cancers

Naita M Wirsik; Pia C Appel; Alexander Braun; Moritz J Strowitzki; Nikolai Schleussner; Henrik Nienhüser; Martin Schneider; Thomas Schmidt

doi:10.1016/j.jss.2024.03.013

Inhibition of the Renin-Angiotensin System Improves Response to Neoadjuvant Therapy in Patients With Liver Metastasis of Colorectal Cancers

J Surg Res. 2024 Apr 14:298:176-184. doi: 10.1016/j.jss.2024.03.013. Online ahead of print.

Authors

Naita M Wirsik¹, Pia C Appel², Alexander Braun³, Moritz J Strowitzki², Nikolai Schleussner², Henrik Nienhüser², Martin Schneider², Thomas Schmidt⁴

Affiliations

¹ Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany; Department of General, Visceral, Cancer and Transplant Surgery, University Hospital of Cologne, Cologne, Germany.
² Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
³ Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany.
⁴ Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany; Department of General, Visceral, Cancer and Transplant Surgery, University Hospital of Cologne, Cologne, Germany. Electronic address: Thomas.Schmidt1@uk-koeln.de.

PMID: 38621351
DOI: 10.1016/j.jss.2024.03.013

Abstract

Introduction: Renin-angiotensin-aldosterone system inhibitors (RAAS-I) have been shown to prolong overall survival in patients with liver metastasized colorectal cancer in combination with antiangiogenic treatment. The effects of RAAS-I combined with neoadjuvant chemotherapy on colorectal cancer liver metastasis remain unexplored. We aimed to study the response of patients undergoing liver resection to RAAS-I in combination with neoadjuvant therapy to elucidate their potential benefits.

Methods: Between February 2005 and May 2012, 62 patients fulfilled the inclusion criteria for distant metastasis (cM1) and comparable computed tomography or magnetic resonance tomography scans in the Picture Archiving Communication System of our center before and after neoadjuvant chemotherapy. Follow-up data and clinicopathological characteristics were collected from a prospective database and retrospectively investigated. The chemotherapeutic response to liver metastasis was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria 1.1.

Results: Comparing the average reduction of measured lesions, a significant response to chemotherapy was detected in the patients receiving RAAS-I (n = 24) compared to those who did not (n = 38) (P = 0.031). Interestingly, the effect was more distinctive when the size reduction was compared between high responses with more than 50% size reduction of all measured lesions (P = 0.011). In the subgroup analysis of patients receiving bevacizumab treatment, high responses to chemotherapy were observed only in the RAAS-I cohort (28.6% versus 0%, P = 0.022).

Conclusions: For neoadjuvantly treated patients, concomitant antihypertensive treatment with RAAS-I showed a higher total size reduction of liver metastasis as a sign of treatment response, especially in combination with antiangiogenic treatment with bevacizumab.

Keywords: Bevacizumab; Chemotherapy; Colorectal cancer; Liver metastasis; Renin-angiotensin aldosterone inhibition.